DOCSLIB.ORG

Alzheimer's Disease (AD) (THC-AD) (THC-AD)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Alzheimer's Disease (AD) (THC-AD) (THC-AD) Alzheimer’s Disease ISSUE BRIEF ON ALZHEIMER’S DISEASE Introduction Briefings such as this one are prepared in response to petitions to add new conditions to the list of qualifying conditions for the Minnesota medical cannabis program. The intention of these briefings is to present to the Commissioner of Health, to members of the Medical Cannabis Review Panel, and to interested members of the public scientific studies of cannabis products as therapy for the petitioned condition. Brief information on the condition and its current treatment is provided to help give context to the studies. The primary focus is on clinical trials and observational studies, but for many conditions there are few of these. A selection of articles on pre-clinical studies (typically laboratory and animal model studies) will be included, especially if there are few clinical trials or observational studies. Though interpretation of surveys is usually difficult because it is unclear whether responders represent the population of interest and because of unknown validity of responses, when published in peer-reviewed journals surveys will be included for completeness. When found, published recommendations or opinions of national organizations medical organizations will be included. Searches for published clinical trials and observational studies are performed using the National Library of Medicine’s MEDLINE database using key words appropriate for the petitioned condition. Articles that appeared to be results of clinical trials, observational studies, or review articles of such studies, were accessed for examination. References in the articles were studied to identify additional articles that were not found on the initial search. This continued in an iterative fashion until no additional relevant articles were found. Finally, the federal government-maintained web site of clinical trials, clinicaltrials.gov, was searched to learn about trials currently under way or under development and to check whether additional articles on completed trials could be found. Definition Alzheimer’s disease (AD) is a neurodegenerative disorder that is distinct from normal aging and is the most common cause of dementia. Dementia refers to a decline in cognition (compared to a previously attained level of cognition) – to the point where it affects day-to-day life and social functioning. This decline is observable as memory loss, diminished reasoning skills and executive functioning (decision-making, planning), and changes to personality/mood and behavior. Neuropathological characteristics of the disease include deposition of β-amyloid (Aβ) into what are called amyloid plaques (amyloidosis) and accumulation of tau protein into neurofibrillary tangles – both of which are implicated in neurodegenerative processes observed in AD brains (Alzheimer’s Association). ISSUE BRIEF – ALZHEIMER’S DISEASE Diagnosis The National Institute on Aging and the Alzheimer’s Association (NIA-AA) recently updated their clinical guidelines for diagnosing AD in 2011. These guidelines generally mirror the typically observed progression of AD, which is: 1) preclinical AD (individual may be undergoing amyloidosis, neurodegeneration, or both processes concurrently, but person is asymptomatic for AD; Sperling et al., 2011), 2) mild cognitive impairment (MCI) due to AD (patient shows signs of cognitive impairment but at levels below a dementia diagnosis; Albert et al., 2011), and 3) clinical AD (McKhann et al., 2011). NIA-AA’s preclinical AD guidelines are a framework for advancing research into identifying preclinical states of AD rather than providing diagnostic criteria for the clinician. Due to research indicating that there are biomarkers for AD (a measurable indicator that may be found within the brain/body (e.g, a substance) that indicates the presence of a particular disease) in the absence of any observable changes, NIA-AA recommends further advancing this area of research to find biomarkers that best predict AD. In addition, they also recognize that there may be subtle cognitive changes in preclinical AD patients—they emphasize the need to develop more sensitive neurocognitive tools to capture these changes to lead to earlier diagnosis. NIA-AA’s criteria for diagnosing mild cognitive impairment (MCI) due to AD include concern being brought to the attention of a clinician regarding a patient’s observed change in cognition (either from the patient, someone who knows the patient well, or the clinician). The patient must also show impairments in at least one cognitive domain that would be greater than what one would expect for someone that age and of their educational background. Furthermore, these impairments cannot be attributed to some other systemic or brain disease. These individuals must still be functioning at a relatively independent level, and they must not fit criteria for a dementia diagnosis. Diagnosis of clinical AD has two main requirements which are to 1) meet core criteria for a dementia diagnosis, and 2) satisfy criteria that would indicate that the cause of dementia is either probably AD (probable AD) or possibly AD (possible AD). Criteria for dementia includes interference in ability to function at usual activities or work, a decline from a previously- attained level of functioning, impairments in cognition as indicated in the patient’s history and through cognitive assessments, and impairments in at least two cognitive domains (acquiring and remembering new information, reasoning/judgment, visuospatial skills, language skills, or changes to personality/behavior). Probable AD criteria includes the observation that symptoms have worsened gradually (months to years as opposed to over a few hours/days) as well as a historical record of this worsening trend, and that cognitive deficits either fall into an amnestic presentation (memory impairments) or non-amnestic presentation (language, visuospatial, executive functioning impairments). Prevalence According to one model of AD prevalence, 6.08 million Americans had AD in 2017 (includes those with mild cognitive impairment due to AD, early clinical AD, and late clinical 2 ISSUE BRIEF – ALZHEIMER’S DISEASE AD). Those numbers are predicted to rise to 15.0 million cases in the US by 2060. According to the same model, 46.7 million Americans were in a preclinical AD state (asymptomatic individuals experiencing amyloidosis, neurodegeneration, or both amyloidosis and neurodegeneration). Preclinical AD cases are expected to rise to 75.68 million by 2060 (Brookmeyer et al., 2018). There are certain risk factors that have been associated with an increased risk of an AD diagnosis. Those who are 60 years old and older are more susceptible to AD (Centers for Disease Control and Prevention; CDC), with 95% of all AD cases identified in patients ≥65 years old (Reitz & Mayeux, 2014). The rate of those with AD doubles every 5 years beyond age 65 (CDC). There also seems to be an inherited risk of developing AD if there are biological family members with the disease (CDC). Other risks include having a cardiovascular disease, Type II diabetes, high blood pressure, excessive body weight, and decreased mental stimulation (Reitz & Mayeux, 2014; CDC) Current Therapies There are currently four FDA-approved pharmacotherapies for treating cognitive and functional decline in AD patients, which are: donepezil, galantamine, rivastigmine, and memantine. The first three are acetylcholine esterase (AChE) inhibitors, while the last one (memantine) is an N-methyl-D-aspartate (NMDA)-receptor antagonist (Anand et al., 2014). AChE inhibiting drugs work by inhibiting the activity of an enzyme (acetylcholine esterase) that breaks down the neurotransmitter acetylcholine (ACh). Dementia is associated with a dysfunctional cholinergic system; therefore, AChE inhibitors are prescribed to enhance ACh levels (by inhibiting AChE, this gives ACh a longer period of time to act on receptor targets). AChE drugs are relatively affordable treatments that are generally well-tolerated (Birks, 2006). While cholinesterase inhibitors appear to be moderately effective in improving cognitive and functional status, the clinical meaningfulness of those changes are sometimes debated in the literature (Livingston et al., 2017; Epperly et al., 2017). In other words, a statistically significant change in dementia symptom scores may not necessarily translate into an observable, clinically significant improvement in dementia. Memantine, as an NMDA-receptor antagonist (NMDA receptor is a glutamatergic receptor), is prescribed due to evidence of glutamatergic excitotoxicity in AD patients. Essentially, too much glutamate release has neurotoxic effects on cells; therefore, memantine works to block NMDA-receptor mediated activity to inhibit the perpetuation of this excessive glutamate release. According to a Cochrane review of memantine on dementia, evidence points to moderate efficacy of this drug on cognition and agitation in moderate to severe Alzheimer’s disease patients and is well tolerated (McShane et al., 2009). Neuropsychiatric symptoms associated with dementia (i.e., depression, agitation) have been treated with antipsychotics (primarily for agitation) and antidepressants (for depression and agitation). However, neuropsychiatric symptoms are poorly managed overall due to low evidence of efficacy (Bains et al., 2002; Nelson & Devanand, 2011) or harms when prescribed to dementia patients. For example, there has been evidence to suggest increased risk of mortality 3 ISSUE BRIEF – ALZHEIMER’S DISEASE
Load more

Recommended publications
  • Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix
    United States International Trade Commission Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix USITC Publication 4208 December 2010 U.S. International Trade Commission COMMISSIONERS Deanna Tanner Okun, Chairman Irving A. Williamson, Vice Chairman Charlotte R. Lane Daniel R. Pearson Shara L. Aranoff Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix Publication 4208 December 2010 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 15, 2010, set forth at the end of this publication, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the United States International Trade Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement changes to the Pharmaceutical Appendix, effective on January 1, 2011. Table 1 International Nonproprietary Name (INN) products proposed for addition to the Pharmaceutical Appendix to the Harmonized Tariff Schedule INN CAS Number Abagovomab 792921-10-9 Aclidinium Bromide 320345-99-1 Aderbasib 791828-58-5 Adipiplon 840486-93-3 Adoprazine 222551-17-9 Afimoxifene 68392-35-8 Aflibercept 862111-32-8 Agatolimod
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9.435,817 B2 Benchikh Et Al
    USOO9435817B2 (12) United States Patent (10) Patent No.: US 9.435,817 B2 Benchikh et al. (45) Date of Patent: Sep. 6, 2016 (54) DETECTION OF SYNTHETIC OTHER PUBLICATIONS CANNABINOIDS C. V. Rao, “Immunology. A textbook”. Alpha Science Internatl. Ltd., 2005, pp. 63, 69-71.* (75) Inventors: Elouard Benchikh, Crumlin (GB); Weissman et al., “Cannabimimetic activity from CP-47,497, a Stephen Peter Fitzgerald, Crumlin derivative of 3-phenylcyclohexanol.” J. Pharmacol. Exp. Ther. (GB); Paul John Innocenzi, Crumlin 1982, vol. 223, No. 2, pp. 516-523.* (GB); Philip Andrew Lowry, Crumlin Wild, “The Immunoassay Handbook.” Third Ed., Elsevier, 2005, (GB); Ivan Robert McConnell, pp. 255-256.* Crumlin (GB) Melvin et al., “A cannabinoid derived prototypical analgesic,” J. Med. Chem., 1984, vol. 27, No. 1, pp. 67-71.* Dresen, S. et al., “Monitoring of Herbal Mixtures Potentially (73) Assignee: Randox Laboratories Limited, Containing Synthetic Cannabinoids as Psychoactive Compounds.” Crumlin (GB) J. Mass. Spectrometry, 2010, pp. 1186-1194, vol. 45. Goodrow, M.H. et al., “Strategies for Immunoassay Hapten (*) Notice: Subject to any disclaimer, the term of this Design,” in Immunoanalysis of Agrochemicals; Nelson, J. et al., patent is extended or adjusted under 35 ACS Symposium Series, 1995, Chapter 9, pp. 119-139, vol. 586. U.S.C. 154(b) by 590 days. Hudson, S. et al., “Use of High-Resolution Accurate Mass Spec trometry to Detect Reported and Previously Unreported Can (21) Appl. No.: 13/585,630 nabinomimetics in Herbal High Products,” J. Anal. Toxicol., 2010, pp. 252-260, vol. 34. Huffman, J. et al., “1-Pentyl-3-phenylacetylindoles, a New Class of (22) Filed: Aug.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0022039 A1 Schwink Et Al
    US 20120022039A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0022039 A1 Schwink et al. (43) Pub. Date: Jan. 26, 2012 (54) NOVEL SUBSTITUTED INDANES, METHOD Publication Classification FOR THE PRODUCTION THEREOF, AND USE (51) Int. Cl. THEREOF AS DRUGS A 6LX 3L/397 (2006.01) C07D 207/06 (2006.01) C07D 2L/22 (2006.01) C07D 22.3/04 (2006.01) (75) Inventors: Lothar Schwink, Frankfurt am C07D 22L/22 (2006.01) Main (DE); Siegfried Stengelin, C07C 235/54 (2006.01) Frankfurt am Main (DE); Matthias C07D 307/14 (2006.01) Gossel, Frankfurt am Main (DE); A63L/35 (2006.01) Klaus Wirth, Frankfurt am Main A6II 3/40 (2006.01) (DE) A6II 3/445 (2006.01) A6II 3/55 (2006.01) A63L/439 (2006.01) A6II 3/66 (2006.01) (73) Assignee: SANOFI, Paris (FR) A6II 3/34 (2006.01) A6IP3/10 (2006.01) A6IP3/04 (2006.01) A6IP3/06 (2006.01) (21) Appl. No.: 13/201410 A6IPL/I6 (2006.01) A6IP3/00 (2006.01) C07D 309/04 (2006.01) (52) U.S. Cl. .................... 514/210.01; 549/426: 548/578; (22) PCT Filed: Feb. 12, 2010 546/205; 540/484; 546/112:564/176; 549/494; 514/459:514/408: 514/319; 514/212.01; 514/299; 514/622:514/471 (86). PCT No.: PCT/EP2010/051796 (57) ABSTRACT The invention relates to substituted indanes and derivatives S371 (c)(1), thereof, to physiologically acceptable salts and physiologi (2), (4) Date: Oct. 4, 2011 cally functional derivatives thereof, to the production thereof, to drugs containing at least one substituted indane according (30) Foreign Application Priority Data to the invention or derivative thereof, and to the use of the Substituted indanes according to the invention and to deriva Feb.
    [Show full text]
  • Potential Cannabis Antagonists for Marijuana Intoxication
    Central Journal of Pharmacology & Clinical Toxicology Bringing Excellence in Open Access Review Article *Corresponding author Matthew Kagan, M.D., Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA, Tel: 310- Potential Cannabis Antagonists 423-3465; Fax: 310.423.8397; Email: Matthew.Kagan@ cshs.org Submitted: 11 October 2018 for Marijuana Intoxication Accepted: 23 October 2018 William W. Ishak, Jonathan Dang, Steven Clevenger, Shaina Published: 25 October 2018 Ganjian, Samantha Cohen, and Matthew Kagan* ISSN: 2333-7079 Cedars-Sinai Medical Center, USA Copyright © 2018 Kagan et al. Abstract OPEN ACCESS Keywords Cannabis use is on the rise leading to the need to address the medical, psychosocial, • Cannabis and economic effects of cannabis intoxication. While effective agents have not yet been • Cannabinoids implemented for the treatment of acute marijuana intoxication, a number of compounds • Antagonist continue to hold promise for treatment of cannabinoid intoxication. Potential therapeutic • Marijuana agents are reviewed with advantages and side effects. Three agents appear to merit • Intoxication further inquiry; most notably Cannabidiol with some evidence of antipsychotic activity • THC and in addition Virodhamine and Tetrahydrocannabivarin with a similar mixed receptor profile. Given the results of this research, continued development of agents acting on cannabinoid receptors with and without peripheral selectivity may lead to an effective treatment for acute cannabinoid intoxication. Much work still remains to develop strategies that will interrupt and reverse the effects of acute marijuana intoxication. ABBREVIATIONS Therapeutic uses of cannabis include chronic pain, loss of appetite, spasticity, and chemotherapy-associated nausea and CBD: Cannabidiol; CBG: Cannabigerol; THCV: vomiting [8]. Recreational cannabis use is on the rise with more Tetrahydrocannabivarin; THC: Tetrahydrocannabinol states approving its use and it is viewed as no different from INTRODUCTION recreational use of alcohol or tobacco [9].
    [Show full text]
  • Medicinal Chemistry Endeavors Around the Phytocannabinoids
    CHEMISTRY & BIODIVERSITY – Vol. 4 (2007) 1707 REVIEW Medicinal Chemistry Endeavors around the Phytocannabinoids by Eric Stern and Didier M. Lambert* Drug Design and Discovery Center and Unite´ de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculte´ de Me´decine, Universite´ catholique de Louvain, Avenue E. Mounier 73, U.C.L. 73.40, B-1200 Bruxelles (phone: þ3227647347; fax: þ3227647363; e-mail: [email protected]) Over the past 50 years, a considerable research in medicinal chemistry has been carried out around the natural constituents of Cannabis sativa L. Following the identification of D9-tetrahydrocannabinol (D9-THC) in 1964, critical chemical modifications, e.g., variation of the side chain at C(3) and the opening of the tricyclic scaffold, have led to the characterization of potent and cannabinoid receptor subtype-selective ligands. Those ligands that demonstrate high affinity for the cannabinoid receptors and good biological efficacy are still used as powerful pharmacological tools. This review summarizes past as well as recent developments in the structure–activity relationships of phytocannabinoids. 1. Introduction. – Despite the wide uses of preparations of the hemp Cannabis sativa L. during the History, the modern pharmacology of natural cannabinoids has been hampered by the slow progress in the elucidations of the chemical structures of its major components. Indeed, it is nowadays known that more than 70 compounds derived from a diterpene structure are present in the plant [1], and this fact may explain the difficulty to obtain pure chemical entities in the past. In addition, the medicinal research for more than a half century has been driven by the search for the components responsible for the psychoactive effects of cannabis, this era in the history of the chemical research on cannabinoids have been recently reviewed [2][3].
    [Show full text]
  • Article 22 Regulation for Restriction of Synthetic Drugs
    ARTICLE 22 REGULATION FOR RESTRICTION OF SYNTHETIC DRUGS SECTION 22.1 AUTHORITY This regulation is promulgated under the authority granted to the Needham Board of Health under Massachusetts General Laws Chapter 111, Section 31 which states that “boards of health may make reasonable health regulations”. SECTION 22.2 PURPOSE The Needham Board of Health has found that synthetic marijuana, consisting of plant or other material treated with various chemicals or other synthetic substances not approved for human consumption, may be marketed and sold as herbal incense in the greater Boston area, although they are being used in the same manner and for the same purposes as scheduled drugs. In addition, the use of these products has become particularly popular among teens and young adults. Based on information and reports from hospitals, emergency room doctors, and police agencies, individuals who use these products experience dangerous side effects including convulsions, hallucinations, and dangerously elevated heart rates. This is evidence that synthetic marijuana products are harmful if inhaled or consumed, and present a significant public health danger. These synthetic compounds and others have a high potential for abuse and lack of any accepted medical use, these dangerous products, while not approved for human consumption, are marketed and sold in a form that allows for such consumption, putting at risk the individuals who come into contact with them. Therefore, the Needham Board of Health adopts this regulation for the purpose and with the intent to protect the public health and safety of the Town of Needham and its residents from the threat posed by the availability and use of synthetic marijuana, synthetic stimulants, synthetic hallucinogens, and other dangerous products by prohibiting persons from trafficking in, possessing, and using them within the town.
    [Show full text]
  • Liver Disease ISSUE BRIEF on LIVER DISEASE
    Liver Disease ISSUE BRIEF ON LIVER DISEASE Introduction Briefings such as this one are prepared in response to petitions to add new conditions to the list of qualifying conditions for the Minnesota medical cannabis program. The intention of these briefings is to present to the Commissioner of Health, to members of the Medical Cannabis Review Panel, and to interested members of the public scientific studies of cannabis products as therapy for the petitioned condition. Brief information on the condition and its current treatment is provided to help give context to the studies. The primary focus is on clinical trials and observational studies, but for many conditions there are few of these. A selection of articles on pre-clinical studies (typically laboratory and animal model studies) will be included, especially if there are few clinical trials or observational studies. Though interpretation of surveys is usually difficult because it is unclear whether responders represent the population of interest and because of unknown validity of responses, when published in peer-reviewed journals surveys will be included for completeness. When found, published recommendations or opinions of national organizations medical organizations will be included. Searches for published clinical trials and observational studies are performed using the National Library of Medicine’s MEDLINE database using key words appropriate for the petitioned condition. Articles that appeared to be results of clinical trials, observational studies, or review articles of such studies, were accessed for examination. References in the articles were studied to identify additional articles that were not found on the initial search. This continued in an iterative fashion until no additional relevant articles were found.
    [Show full text]
  • 2 Spice English Presentation
    Spice Spice contains no compensatory substances Специи не содержит компенсационные вещества Spice is a mix of herbs (shredded plant material) and manmade chemicals with mind-altering effects. It is often called “synthetic marijuana” because some of the chemicals in it are similar to ones in marijuana; but its effects are sometimes very different from marijuana, and frequently much stronger. It is most often labeled “Not for Human Consumption” and disguised as incense. Eliminationprocess • The synthetic agonists such as THC is fat soluble. • Probably, they are stored as THC in cell membranes. • Some of the chemicals in Spice, however, attach to those receptors more strongly than THC, which could lead to a much stronger and more unpredictable effect. • Additionally, there are many chemicals that remain unidentified in products sold as Spice and it is therefore not clear how they may affect the user. • Moreover, these chemicals are often being changed as the makers of Spice alter them to avoid the products being illegal. • To dissolve the Spice crystals Acetone is used endocannabinoids synhtetic THC cannabinoids CB1 and CB2 agonister Binds to cannabinoidreceptor CB1 CB2 - In the brain -in the immune system Decreased avtivity in the cell ____________________ Maria Ellgren Since some of the compounds have a longer toxic effects compared to naturally THC, as reported: • negative effects that often occur the day after consumption, as a general hangover , but without nausea, mentally slow, confused, distracted, impairment of long and short term memory • Other reports mention the qualitative impairment of cognitive processes and emotional functioning, like all the oxygen leaves the brain.
    [Show full text]
  • Shlomi Cohen, Israel Manela, Eli More , Et Al. V. Pharmos Corp. , Et Al
    UNITED STATES DISTRICT COURT DISTRICT OF NEW JERSEY _____________________________________ ) SHLOMI COHEN, ISRAEL MANELA, and ELI ) Case No. ____________ MORE, individually and on behalf of all others ) similarly situated, ) ) CLASS ACTION COMPLAINT ) Plaintiffs, ) ) JURY TRIAL DEMANDED v. ) ) HAIM AVIV; GAD RIESENFELD; and PHARMOS ) CORP., ) ) Defendants. ) _____________________________________ ) Plaintiffs, by undersigned counsel, for plaintiffs’ Class Action Complaint, allege the following upon personal knowledge as to plaintiffs and plaintiffs’ own acts, and upon information and belief based upon the investigation of plaintiffs’ attorneys as to all other matters. The investigation includes the review and analysis of public statements and publicly-filed documents of Pharmos Corp. ("Pharmos" or the "Company"), press releases, news articles and related literature. Plaintiffs believe that further substantial evidentiary support will exist for the allegations set forth below after a reasonable opportunity for discovery. SUMMARY OF ACTION 1. This is a securities class action on behalf of investors who purchased common stock of the Pharmos during the period from August 23, 2004 through December 17, 2004 (the "Class Period"). 2. Pharmos is a bio-pharmaceutical company that develops drugs to treat a range of neuro-inflammatory disorders. Pharmos’s main product, Dexanabinol, is a synthetic non- psychotropic cannabinoid for the treatment of traumatic brain injury. 3. Pharmos’s common stock is listed on the Nasdaq under the ticker symbol “PARS”; and as of November 1, 2004, Pharmos had 94.3 million shares outstanding. 4. Throughout the Class Period, defendants repeatedly touted Dexanabinol, causing Pharmos’ stock price to climb dramatically. In fact, Dexanabinol was simply ineffective in treating Traumatic Brain Injury, and defendants were aware of or recklessly disregarded evidence of that ineffectiveness.
    [Show full text]
  • Long Term Cerebroprotective Effects of Dexanabinol in a Model of Focal Cerebral Ischemia Gil Lavieaa,Cbaa, , Angella Teichner , Esther Shohami , Haim Ovadia , Ronen R
    Brain Research 901 (2001) 195±201 www.elsevier.com/locate/bres Research report Long term cerebroprotective effects of dexanabinol in a model of focal cerebral ischemia Gil Lavieaa,cbaa, , Angella Teichner , Esther Shohami , Haim Ovadia , Ronen R. Leker * aDepartment of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical School, Hadassah University Hospital, Ein Kerem, P.O. Box 12000, Jerusalem 91120, Israel bDepartment of Pharmacology, Hebrew University-Hadassah Medical School, Hadassah University Hospital, Jerusalem, Israel cDepartment of Neurological Sciences, University of Rome, La Sapienza, Rome, Italy Accepted 27 February 2001 Abstract In order to test the long-term cerebroprotective effects of dexanabinol, a synthetic non-competitive NMDA antagonist that also has anti-TNFa effects, spontaneously hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO). Rats were given vehicle or dexanabinol (4.5 mg/kg) 1, 3 or 6 h after PMCAO. The research consisted of 2 stages. In the short-term set of experiments animals (n55/group), were tested with a motor disability scale 24 h post PMCAO, then sacri®ced and the infarct volume was measured using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. In the long-term set of experiments the rats (n57/group) were examined daily with a motor disability scale up to 30 days after PMCAO and then sacri®ced and infarct volumes were determined using TTC staining. Motor scores were signi®cantly improved in the dexanabinol treated rats (P,0.05 for all groups) at all the time points examined. Infarct volumes were signi®cantly reduced 24 h after PMCAO in the groups treated 1 or 3 h, but not 6 h after PMCAO compared with vehicle (Mean6S.D., 11.562.02, 1263.2 and 14.462.4% vs.
    [Show full text]
  • Cannabinoid Receptor Cannabinoid Receptor
    Cannabinoid Receptor Cannabinoid Receptor Cannabinoid receptors are currently classified into three groups: central (CB1), peripheral (CB2) and GPR55, all of which are G-protein-coupled. CB1 receptors are primarily located at central and peripheral nerve terminals. CB2 receptors are predominantly expressed in non-neuronal tissues, particularly immune cells, where they modulate cytokine release and cell migration. Recent reports have suggested that CB2 receptors may also be expressed in the CNS. GPR55 receptors are non-CB1/CB2 receptors that exhibit affinity for endogenous, plant and synthetic cannabinoids. Endogenous ligands for cannabinoid receptors have been discovered, including anandamide and 2-arachidonylglycerol. www.MedChemExpress.com 1 Cannabinoid Receptor Antagonists, Agonists, Inhibitors, Modulators & Activators (S)-MRI-1867 (±)-Ibipinabant Cat. No.: HY-141411A ((±)-SLV319; (±)-BMS-646256) Cat. No.: HY-14791A (S)-MRI-1867 is a peripherally restricted, orally (±)-Ibipinabant ((±)-SLV319) is the racemate of bioavailable dual cannabinoid CB1 receptor and SLV319. (±)-Ibipinabant ((±)-SLV319) is a potent inducible NOS (iNOS) antagonist. (S)-MRI-1867 and selective cannabinoid-1 (CB-1) receptor ameliorates obesity-induced chronic kidney disease antagonist with an IC50 of 22 nM. (CKD). Purity: >98% Purity: 99.93% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg 2-Arachidonoylglycerol 2-Palmitoylglycerol Cat. No.: HY-W011051 (2-Palm-Gl) Cat. No.: HY-W013788 2-Arachidonoylglycerol is a second endogenous 2-Palmitoylglycerol (2-Palm-Gl), an congener of cannabinoid ligand in the central nervous system. 2-arachidonoylglycerol (2-AG), is a modest cannabinoid receptor CB1 agonist. 2-Palmitoylglycerol also may be an endogenous ligand for GPR119.
    [Show full text]
  • How Is Spice Abused? What Are the Health Effects of Spice Abuse?
    Spice “Spice” is used to describe a diverse What Are the Health Effects family of herbal mixtures marketed under of Spice Abuse? many names, including K2, fake marijuana, Presently, there are no studies on the effects Yucatan Fire, Skunk, Moon Rocks, and of Spice on human health or behavior. A others. These products contain dried, variety of mood and perceptual effects have shredded plant material and presumably, been described, and patients who have been chemical additives that are responsible for taken to Poison Control Centers in Texas their psychoactive (mind-altering) effects. report symptoms that include rapid heart While Spice products are labeled “not for rate, vomiting, agitation, confusion, and human consumption” they are marketed hallucinations. to people who are interested in herbal alternatives to marijuana (cannabis). Spice Public Health Concerns users report experiences similar to those produced by marijuana, and regular users Marketing labels often make unverified may experience withdrawal and addiction claims that Spice products contain up to 3.0 symptoms. grams of a natural psychoactive material taken from a variety of plants. While Spice Spice mixtures are sold in many countries products do contain dried plant material, in head shops, gas stations, and via the chemical analyses of seized spice mixtures Internet, although their sale and use are have revealed the presence of synthetic (or illegal throughout most European countries. designer) cannabinoid compounds.* These Easy access has likely contributed to Spice’s bind to the same cannabinoid receptors in the popularity. body as THC (delta-9-tetrahydrocannabinol), the primary psychoactive component of How Is Spice Abused? marijuana.
    [Show full text]